Incremental Hemodialysis for Veterans in the First Year of Dialysis (IncHVets): A Pragmatic, Multi-Center, Randomized Controlled Trial

退伍军人透析第一年增量血液透析 (IncHVets)：一项务实、多中心、随机对照试验

• 批准号: 10486289
• 负责人: Kamyar Kalantar-Zadeh
• 金额: --
• 依托单位: VETERANS HEALTH ADMINISTRATION
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-10-01 至 2027-09-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10486289
• 关键词: Address; Adverse event; American; Ancillary Study; Blood Vessels; Cachexia; Cardiac; Cardiovascular system; Caregiver Burden; Caring; Client satisfaction; Clinic; Clinic Visits; Clinical; Clinical Trials; Costs and Benefits; Dialysis patients; Dialysis procedure; Dose; Eating; Eligibility Determination; Emergency department visit; End stage renal failure; Event; Fatigue; Frequencies; Future; GDF15 gene; Growth; Healthcare Systems; Hemodialysis; Hospitalization; Human Resources; Hypotension; Hypotensives; Impaired health; Inflammation; Inflammatory; Injury to Kidney; Intervention; Kidney; Kidney Diseases; Left; Left Ventricular Mass; Life; Longevity; Maintenance; Malnutrition; Measures; Medical center; Muscle; Nutritional; Nutritional status; Organ; Outcome; Outcome Measure; Outpatients; Output; Parents; Patient Outcomes Assessments; Patients; Physical Function; Physical Performance; Population; Pragmatic clinical trial; Proteins; Protocols documentation; Provider; Randomized, Controlled Trials; Regimen; Renal function; Research Design; Research Personnel; Residual state; Resources; Safety; Schedule; Serum; Site; Symptoms; System; Testing; Time; Time trend; Urea; Urine; Veterans; Veterans Health Administration; Withdrawal; arm; coping; cost; design; experience; frailty; functional status; health care service utilization; health related quality of life; hyperkalemia; improved; indexing; mortality; mortality risk; muscle form; nutrition; physical conditioning; pragmatic study; precision medicine; preference; preservation; primary endpoint; primary outcome; safety assessment; safety outcomes; safety testing; scale up; secondary endpoint; secondary outcome; standard of care; survival prediction; wasting

PROJECT SUMMARY Each year approximately 12,000 Veterans develop end-stage renal disease (ESRD) and initiate dialysis treatment. These patients comprise >10% of the US incident ESRD population. Dialysis is costly and associated with impaired health-related quality of life (HRQOL) and high mortality risk, particularly in the first dialysis year. The current paradigm is to start treatment with full-dose thrice-weekly hemodialysis (HD) irrespective of patients' residual kidney function (RKF), and this abrupt transition increases patients' and care- partners' burden and suffering and may limit their preferences. Furthermore, recent evidence suggests that Veterans who receive dialysis in a VA center have greater survival compared to those treated in non-VA units. Although not currently the standard of care, evidence suggests that a gradual or incremental dialysis transition using an initial twice-weekly HD schedule may confer substantial benefits including more dialysis- free time, longer RKF preservation, vascular access longevity, less intradialytic hypotension and end-organ damage, reduced post-dialysis fatigue, and less patient suffering. Hence, an incremental dialysis transition may result in improved HRQOL through improved physical function, less fatigue, greater energy, and improved patient satisfaction and life participation by mitigating the burden of excessive dialysis in daily life. Pragmatic studies with immediate clinical impact are urgently needed to shift the focus of dialysis from an abrupt thrice-weekly HD start to a safe and effective personalized dialysis regimen. Moreover, implementing a twice-weekly HD schedule would allow 20% more Veterans to receive care within a VA-based dialysis unit. In the spirit of RFA CX-21-006 for clinical trials, in this multiple-PI, multi-site, pragmatic, 1:1 randomized controlled trial (RCT), parallel with Veterans' routine dialysis therapy, we will test the safety and efficacy of an incremental twice-weekly HD protocol, compared to standard-of-care thrice-weekly HD, in Veterans who meet predefined eligibility criteria. We plan to compare twice-weekly (incremental) with thrice-weekly (conventional) HD initiation in 252 Veterans with incident ESRD, who will transition to maintenance HD therapy in six VA centers. Using quarterly assessments for up to 12 months, we will examine the Short Form 36 (SF36) HRQOL physical component score as the primary outcome, as well as Dialysis Symptom Index and SF36 energy/ fatigue score as secondary endpoints. Additional secondary outcomes will include preservation of RKF, dialysis adequacy, nutritional status, and protein-energy wasting markers to be measured quarterly. Safety assessments will include mortality, dialysis withdrawals, emergency room visits, hospitalizations, hyperkalemia, and major adverse cardiovascular events. In a substudy examining exploratory outcomes in 112 Veterans from three VA centers in the parent trial, we will also examine of cardiac measures including left ventricular mass, as well as nutritional/physical function indices of muscle mass and physical performance. Our proposed pragmatic RCT addresses a major unmet need in Veterans with incident ESRD initiating dialysis by focusing on improving HRQOL and preserving RKF, the two strongest predictors of survival and patient satisfaction. The results of this study may enable more Veterans to receive therapy in a VA based dialysis center. Our study may lead to a paradigm shift with immediate impact on kidney care in Veterans and in the broader ESRD population. The pragmatic design will permit a rapid scaling-up of the interventions in larger settings since the RCT takes advantage of resources and personnel that are readily available in VA centers under experienced investigators and clinicians across multiple VA sites nationwide. This proposed study challenges the current standard of care of outright thrice weekly HD in the first year of dialysis therapy, during which patients' suffering and mortality are the highest, and is less likely to be supported by for-profit dialysis providers given the perceived reduction in revenue if twice-weekly HD is to be implemented broadly.

项目概要 每年约有 12,000 名退伍军人出现终末期肾病 (ESRD) 并开始透析 治疗。这些患者占美国 ESRD 发病人群的 10% 以上。透析费用昂贵且 与健康相关的生活质量 (HRQOL) 受损和高死亡风险相关，尤其是在第一 透析年。目前的范例是开始每周三次全剂量血液透析 (HD) 治疗 无论患者的残余肾功能（RKF）如何，这种突然的转变都会增加患者和护理的负担 伴侣的负担和痛苦，并可能限制他们的偏好。此外，最近的证据表明 与在非退伍军人事务部接受透析的退伍军人相比，在退伍军人事务部中心接受透析的退伍军人的生存率更高。 虽然目前不是护理标准，但有证据表明渐进或增量透析 使用最初的每周两次 HD 计划进行过渡可能会带来巨大的好处，包括更多的透析- 自由时间、更长的 RKF 保存、血管通路寿命更长、透析中低血压和终末器官减少 损害，减少透析后疲劳，并减少患者痛苦。因此，增量透析过渡 可能会通过改善身体机能、减少疲劳、增加精力和提高 HRQOL 通过减轻日常生活中过度透析的负担，提高患者满意度和生活参与度。 迫切需要具有直接临床影响的务实研究，以将透析的重点从 突然每周三次 HD 开始安全有效的个性化透析方案。此外，实施 每周两次的 HD 计划将使 20% 的退伍军人能够在 VA 透析中心接受护理。 本着 RFA CX-21-006 临床试验的精神，在这个多 PI、多地点、务实、1:1 随机 对照试验（RCT），与退伍军人的常规透析治疗并行，我们将测试一种药物的安全性和有效性 与标准护理每周三次 HD 相比，在满足以下条件的退伍军人中增加每周两次 HD 方案 预定义的资格标准。我们计划将每周两次（增量）与每周三次（传统）进行比较 252 名患有终末期肾病 (ESRD) 的退伍军人开始接受 HD 治疗，其中 6 名退伍军人将过渡到维持 HD 治疗 中心。我们将使用长达 12 个月的季度评估来检查简表 36 (SF36) HRQOL 身体成分评分作为主要结果，以及透析症状指数和 SF36 能量/ 疲劳评分作为次要终点。其他次要结果将包括保留 RKF、 每季度测量一次透析充分性、营养状况和蛋白质-能量消耗指标。安全 评估将包括死亡率、透析退出、急诊室就诊、住院治疗、 高钾血症和主要不良心血管事件。在一项检查探索性结果的子研究中 在母试验中，来自三个 VA 中心的 112 名退伍军人，我们还将检查心脏测量值，包括左 心室质量，以及肌肉质量和身体表现的营养/身体功能指数。 我们提出的务实随机对照试验解决了退伍军人因事件终末期肾病（ESRD）而未得到满足的主要需求 通过专注于改善 HRQOL 和保留 RKF（生存和生存的两个最强预测因子）进行透析 患者满意度。这项研究的结果可能使更多的退伍军人能够在 VA 的基础上接受治疗 透析中心。我们的研究可能会导致范式转变，对退伍军人和老年人的肾脏护理产生直接影响 在更广泛的 ESRD 人群中。务实的设计将允许快速扩大干预措施 更大的环境，因为 RCT 利用了 VA 现有的资源和人员 中心由经验丰富的研究人员和临床医生负责，遍布全国多个 VA 站点。这个提议 研究挑战了透析治疗第一年每周三次 HD 的现行护理标准， 在此期间患者的痛苦和死亡率最高，并且不太可能得到营利性支持 考虑到如果广泛实施每周两次 HD，透析提供商的收入将会减少。